INS and obesity due to melanocortin 4 receptor deficiency: Hepatocyte mitochondria are essential for the maintenance of metabolic plasticity and flexibility (Koliaki and Roden, 2016), and consistent with this, recent studies have shown that mouse models of hepatic mitochondrial dysfunction have alterations in their systemic metabolism, including changes in insulin sensitivity, energy expenditure (EE), and their response to diet-induced obesity (Cho et al., 2017; Kulkarni et al., 2016; Lee et al., 2017; Pospisilik et al., 2007).